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Gut Microbial Metabolites and Future Risk of Parkinson's Disease: A Metabolome-Wide Association Study.

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dc.contributor.authorZhao, Yujia
dc.contributor.authorLai, Yunjia
dc.contributor.authorDarweesh, Sirwan K L
dc.contributor.authorBloem, Bastiaan R
dc.contributor.authorForsgren, Lars
dc.contributor.authorHansen, Johnni
dc.contributor.authorKatzke, Verena A
dc.contributor.authorMasala, Giovanna
dc.contributor.authorSieri, Sabina
dc.contributor.authorSacerdote, Carlotta
dc.contributor.authorPanico, Salvatore
dc.contributor.authorZamora-Ros, Raul
dc.contributor.authorSanchez-Perez, Maria-Jose
dc.contributor.authorHuerta, José María
dc.contributor.authorGuevara, Marcela
dc.contributor.authorVinagre-Aragon, Ana
dc.contributor.authorVineis, Paolo
dc.contributor.authorLill, Christina M
dc.contributor.authorMiller, Gary W
dc.contributor.authorPeters, Susan
dc.contributor.authorVermeulen, Roel
dc.contributor.authoraffiliation[Sanchez-Perez,MJ] Escuela Andaluza de Salud Pública (EASP), Granada, Spain.
dc.contributor.authoraffiliation[Sanchez-Perez,MJ] Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain.
dc.contributor.authoraffiliation[Sanchez-Perez,MJ] Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
dc.contributor.funderAgency for Research on Cancer
dc.contributor.funderDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London
dc.contributor.funderNational Institute for Health and Care Research Imperial Biomedical Research Centre (BRC
dc.contributor.funderChina Scholarship Council
dc.contributor.funderParkinson’s Foundation
dc.contributor.funderInstituto de Salud Carlos III (ISCIII)
dc.contributor.funderRegional Governments of Andalucía
dc.date.accessioned2024-11-25T11:50:31Z
dc.date.available2024-11-25T11:50:31Z
dc.date.issued2024-11-12
dc.description.abstractBackground Alterations in gut microbiota are observed in Parkinson's disease (PD). Previous studies on microbiota-derived metabolites in PD were small-scale and post-diagnosis, raising concerns about reverse causality. Objectives Our goal was to prospectively investigate the association between plasma microbial metabolites and PD risk within a metabolomics framework. Methods A nested case–control study within the prospective EPIC4PD cohort, measured pre-diagnostic plasma microbial metabolites using untargeted metabolomics. Results Thirteen microbial metabolites were identified nominally associated with PD risk (P-value < 0.05), including amino acids, bile acid, indoles, and hydroxy acid, although none remained significant after multiple testing correction. Three pathways were implicated in PD risk: valine, leucine, and isoleucine degradation, butanoate metabolism, and propanoate metabolism. PD-associated microbial pathways were more pronounced in men, smokers, and overweight/obese individuals. Conclusion Changes in microbial metabolites may represent a pre-diagnostic feature of PD. We observed biologically plausible associations between microbial pathways and PD, potentially influenced by individual characteristics. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
dc.description.sponsorshipThis work was supported by Stichting ParkinsonFonds. Y.Z. received support from the China Scholarship Council during the PhD period at Utrecht University-Institute for Risk Assessment Sciences. S.K.L.D. has received funding from the Parkinson’s Foundation (PFFBS-2026), ZonMW (09150162010183), ParkinsonNL (P2022-07 and P2021-14), The Michael J. Fox Foundation (MJFF-022767), and Edmond J Safra Foundation. C.M.L. was supported by the Heiseberg programme of the Deutsche Forschungsgemeinschaft (DFG; LI 2654/4-1) and by The Michael J. Fox Foundation (MJFF-008994). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the National Institute for Health and Care Research Imperial Biomedical Research Centre (BRC). We are grateful to all the participants who have been part of the project. We acknowledge Dr. Miles Trupp from the Department of Clinical Science, Neurosciences, Umeå University, for his review of the manuscript, particularly for the interpretation on microbial metabolite functions. The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (France); German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam-Rehbruecke, Federal Ministry of Education and Research (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports, National Institute for Public Health and the Environment, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund, Statistics Netherlands (The Netherlands); Health Research Fund (FIS)— Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, the Catalan Institute of Oncology—ICO, CERCA Program/Generalitat de Catalunya for the institutional support to IDIBELL (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (C864/A14136 to EPIC-Norfolk; C8221/A29017 to EPICOxford), Medical Research Council (MR/N003284/1, MC-UU_12015/1, and MC_UU_00006/1 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford), University of Cambridge (UK).
dc.description.versionYes
dc.identifier.citationZhao Y, Lai Y, Darweesh SKL, Bloem BR, Forsgren L, Hansen J, et al. Gut Microbial Metabolites and Future Risk of Parkinson's Disease: A Metabolome-Wide Association Study. Mov Disord. 2024 Nov 12.
dc.identifier.doi10.1002/mds.30054
dc.identifier.essn1531-8257
dc.identifier.pmid39530417
dc.identifier.urihttps://hdl.handle.net/10668/24332
dc.journal.titleMovement disorders : official journal of the Movement Disorder Society
dc.language.isoen
dc.page.number14
dc.publisherRaven Press
dc.relation.projectIDPFFBS-2026
dc.relation.projectIDP2022-07
dc.relation.projectIDP2021-14
dc.relation.projectIDMJFF-022767
dc.relation.projectIDDFG; LI 2654/4-1
dc.relation.projectIDMJFF-008994
dc.relation.projectIDC864/A14136
dc.relation.publisherversionhttps://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.30054
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectGut‐brain axis
dc.subjectMicrobial metabolites
dc.subjectParkinson's disease
dc.subjectPre‐diagnostic biosamples
dc.subjectUntargeted metabolomics
dc.subject.decsEnfermedad de Parkinson
dc.subject.decsMicrobioma Gastrointestinal
dc.subject.decsDiagnóstico
dc.subject.decsIsoleucina
dc.subject.meshParkinson Disease
dc.subject.meshMicrobiota
dc.subject.meshGastrointestinal Microbiome
dc.titleGut Microbial Metabolites and Future Risk of Parkinson's Disease: A Metabolome-Wide Association Study.
dc.typeresearch article
dc.type.hasVersionVoR
dspace.entity.typePublication

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